Submissions for variant NM_001042492.3(NF1):c.503C>G (p.Ser168Ter)

dbSNP: rs1131691994

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493132	SCV000583314	pathogenic	not provided	2017-05-31	criteria provided, single submitter	clinical testing	The S168X nonsense variant in the NF1 gene has been observed previously in a patient with neurofibromatosis type 1; the variant is not listed in the publication itself but is listed in the Human Gene Mutation Database and was noted to be obtained via personal communication (vanMinkelen et al., 2014; Stenson et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, we consider this variant to be pathogenic.
Invitae	RCV000707168	SCV000836253	pathogenic	Neurofibromatosis, type 1	2024-01-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser168*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 430497). For these reasons, this variant has been classified as Pathogenic.
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital	RCV001009566	SCV001169667	pathogenic	Neurofibromatosis, type 1; Tibial pseudarthrosis	2018-11-10	criteria provided, single submitter	research
Genome-Nilou Lab	RCV000707168	SCV002561581	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000493132	SCV002771577	pathogenic	not provided	2021-07-17	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant was not reported in large, multi-ethnic, general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital	RCV000707168	SCV001482377	pathogenic	Neurofibromatosis, type 1	2019-05-31	no assertion criteria provided	research